Rhonda Souza M.D.

Que, J., K. S. Garman, R. F. Souza and S. J. Spechler (2019). “Pathogenesis and Cells of Origin of Barrett’s Esophagus.” Gastroenterology May 10. [Epub ahead of print].

Full text of this article.

In patients with Barrett’s esophagus (BE), metaplastic columnar mucosa, containing epithelial cells with gastric and intestinal features, replaces esophageal squamous mucosa damaged by gastroesophageal reflux disease. This condition is estimated to affect 5.6% of adults in the United States, and is a major risk factor for esophageal adenocarcinoma. Despite the prevalence and importance of BE, its pathogenesis is incompletely understood and there are disagreements over the cells of origin. We review mechanisms of BE pathogenesis, including transdifferentiation and transcommitment, and discuss potential cells of origin including basal cells of the squamous epithelium, cells of esophageal submucosal glands and their ducts, cells of the proximal stomach, and specialized populations of cells at the esophago-gastric junction (residual embryonic cells and transitional basal cells). We discuss the concept of metaplasia as a wound-healing response, and how cardiac mucosa might be the precursor of the intestinal metaplasia of BE. Finally, we discuss shortcomings in current diagnostic criteria for BE that have important clinical implications.

Peters, Y., A. Al-Kaabi, N. J. Shaheen, A. Chak, A. Blum, R. F. Souza, M. Di Pietro, P. G. Iyer, O. Pech, R. C. Fitzgerald and P. D. Siersema (2019). “Barrett oesophagus.” Nat Rev Dis Primers 5(1): 35.

Full text of this article.

Barrett oesophagus (BE), the only known histological precursor of oesophageal adenocarcinoma (EAC), is a condition in which the squamous epithelium of the oesophagus is replaced by columnar epithelium as an adaptive response to gastro-oesophageal reflux. EAC has one of the fastest rising incidences of cancers in Western countries and has a dismal prognosis. BE is usually detected during endoscopic examination, and diagnosis is confirmed by the histological presence of intestinal metaplasia. Advances in genomics and transcriptomics have improved our understanding of the pathogenesis and malignant progression of intestinal metaplasia. As the majority of EAC cases are diagnosed in individuals without a known history of BE, screening for BE could potentially decrease disease-related mortality. Owing to the pre-malignant nature of BE, endoscopic surveillance of patients with BE is imperative for early detection and treatment of dysplasia to prevent further progression to invasive EAC. Developments in endoscopic therapy have resulted in a major shift in the treatment of patients with BE who have dysplasia or early EAC, from surgical resection to endoscopic resection and ablation. In addition to symptom control by optimization of lifestyle and pharmacological therapy with proton pump inhibitors, chemopreventive strategies based on NSAIDs and statins are currently being investigated for BE management.

Snyder, P., K. Dunbar, D. J. Cipher, R. F. Souza, S. J. Spechler and V. J. A. Konda (2019). “Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses.” Dig Dis Sci 64(5): 1089-1097.

Full text of this article.

Risk stratification of patients with Barrett’s esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p < .001 (95% CI 2.79-5.27) and OR 5.95, p < .001 (95% CI 2.68-13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p < .001 (95% CI 9.35-32.08) and RR = 14.25, p < .001 (95% CI 6.76-30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients.

Snyder, P., K. Dunbar, D. J. Cipher, R. F. Souza, S. J. Spechler and V. J. A. Konda (2019). “Aberrant p53 Immunostaining in Barrett’s Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses.” Dig Dis Sci Mar 26. [Epub ahead of print].

Full text of this article.

Risk stratification of patients with Barrett’s esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p < .001 (95% CI 2.79-5.27) and OR 5.95, p < .001 (95% CI 2.68-13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p < .001 (95% CI 9.35-32.08) and RR = 14.25, p < .001 (95% CI 6.76-30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients.

Kobashigawa, J., D. Dadhania, S. Bhorade, D. Adey, J. Berger, G. Bhat, M. Budev, A. Duarte-Rojo, M. Dunn, S. Hall, M. N. Harhay, K. L. Johansen, S. Joseph, C. C. Kennedy, E. Kransdorf, K. L. Lentine, R. J. Lynch, M. McAdams-DeMarco, S. Nagai, M. Olymbios, J. Patel, S. Pinney, J. Schaenman, D. L. Segev, P. Shah, L. G. Singer, J. P. Singer, C. Sonnenday, P. Tandon, E. Tapper, S. G. Tullius, M. Wilson, M. Zamora and J. C. Lai (2019). “Report from the American Society of Transplantation on frailty in solid organ transplantation.” Am J Transplant 19(4): 984-994.

Full text of this article.

A consensus conference on frailty in kidney, liver, heart, and lung transplantation sponsored by the American Society of Transplantation (AST) and endorsed by the American Society of Nephrology (ASN), the American Society of Transplant Surgeons (ASTS), and the Canadian Society of Transplantation (CST) took place on February 11, 2018 in Phoenix, Arizona. Input from the transplant community through scheduled conference calls enabled wide discussion of current concepts in frailty, exploration of best practices for frailty risk assessment of transplant candidates and for management after transplant, and development of ideas for future research. A current understanding of frailty was compiled by each of the solid organ groups and is presented in this paper. Frailty is a common entity in patients with end-stage organ disease who are awaiting organ transplantation, and affects mortality on the waitlist and in the posttransplant period. The optimal methods by which frailty should be measured in each organ group are yet to be determined, but studies are underway. Interventions to reverse frailty vary among organ groups and appear promising. This conference achieved its intent to highlight the importance of frailty in organ transplantation and to plant the seeds for further discussion and research in this field.